The lactate receptor HCAR1: A key modulator of epileptic seizure activity.

ABSTRACT: Epilepsy affects millions globally with a significant portion exhibiting pharmacoresistance. Abnormal neuronal activity elevates brain lactate levels, which prompted the exploration of its receptor, the hydroxycarboxylic acid receptor 1 (HCAR1) known to downmodulate neuronal activity in physiological conditions. This study revealed that HCAR1-deficient mice (HCAR1-KO) exhibited lowered seizure thresholds, and increased severity and duration compared to wild-type mice. Hippocampal and whole-brain electrographic seizure analyses revealed increased seizure severity in HCAR1-KO mice, supported by time-frequency analysis. The absence of HCAR1 led to uncontrolled inter-ictal activity in acute hippocampal slices, replicated by lactate dehydrogenase A inhibition indicating that the activation of H

SUBMITTER: Alessandri M 

PROVIDER: S-EPMC11035371 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature